Needs and views on eye health and women's empowerment and theory of change map: implication on the development of a women-targeted eyecare programme for older Zanzibari craftswomen.

OBJECTIVES: To assess needs and views regarding eye health and empowerment from craftswomen's perspectives to develop a theory of change (ToC) for a women-targeted eyecare programme. MATERIAL AND METHODS: Eighteen stakeholders participated in a 2-day consultation workshop in Zanzibar. The composition was (1) 15 women and 3 men; (2) Unguja (n=8), Pemba (n=6) and Tanzania mainland (n=4) and (3) craftswomen (n=14) and governmental stakeholders (n=4). Thematic analysis determined the craftswomen's needs and views regarding eye health and empowerment and subsequently inputs, activities, outputs, outcomes and impact to develop the programme's initial ToC. In refining the initial ToC, we used insights from a qualitative study suggesting that improved near vision is perceived by craftswomen as a potential source of empowerment across economic, psychological, social, political and educational dimensions. RESULTS: The eye conditions experienced by the craftswomen were eye irritation caused by foreign bodies, the need for near spectacles and other eye morbidities. They were advised by the cooperatives to visit eye health centres for treatment. The main barriers to accessing services were inaccessibility and unaffordability of eye services and a lack of eye health knowledge and practices. Nineteen subthemes on women empowerment (economic n=4, social n=4, psychological n=6, education n=2 and political n=3) were obtained. We created a ToC on how investing in improving craftswomen near vision could achieve empowerment. CONCLUSION: The participants provided insights into their needs and how they would like the eyecare programme to be implemented and how they see they could be empowered in the process.

Subjective Wellbeing, Work Performance and Lived Experience of Zanzibari Women Entrepreneurs with Uncorrected Functional Presbyopia: A Pre-Post Mixed-Methods Study.

PURPOSE: Uncorrected presbyopia has been shown to reduce Zanzibari women's quality of life. In this mixed-methods study, we examined the subjective wellbeing and self-reported work performance among older women entrepreneurs with functional presbyopia before and shortly after correction, and how poor vision at close distance affected their daily lives. METHODS: Women entrepreneurs underwent eye examination to identify those with uncorrected functional presbyopia. Their subjective wellbeing and work performance were both measured in Cantril's ladder. Ready-made glasses were then provided and 30 minutes to an hour later, their subjective wellbeing and work performance was remeasured. Twenty women entrepreneurs were interviewed to understand their lived experience with uncorrected presbyopia. RESULTS: Two-hundred-seventeen women entrepreneurs were included in the survey (mean age 51.6 years, SD 8.64). Women entrepreneurs had a mean subjective wellbeing score of 3.32 (SD 1.10) pre-correction and 5.99 (SD 1.13) post-correction (p < .001), and a mean self-rated current work performance score of 4.62 (SD 1.36) before correction and 5.47 (SD 1.35) post-correction (p < .001). One-hundred-and-ninety (87.6%) and 121 women entrepreneurs (55.8%) rated their current subjective wellbeing and work performance scores < 5, respectively. Around 1/4 of women entrepreneurs reported having severe difficulties with near tasks. CONCLUSION: Poor vision at a close distance caused by uncorrected functional presbyopia negatively affected economic, physical and psychosocial aspects of women entrepreneurs' lives. Subjective wellbeing and self-reported work productivity scores improved significantly shortly after presbyopia was corrected. More research with longer follow-up is needed to understand the full benefits of correcting presbyopia.

Refractive error, eye care needs and attitude towards spectacle wearing among older Zanzibari craftswomen and implications for developing women-targeted services: a cross-sectional study.

BACKGROUND: Aged Zanzibari women are in a disadvantaged position, having high demand for near-vision spectacles. Currently, there is no information on the eye health status of craftswomen, which makes planning a women-targeted project to deliver eye health services to older craftswomen in Zanzibar difficult. We assessed the prevalence of vision impairment, refractive error, presbyopia, effective spectacle coverage (distance and near) and attitude towards spectacle wearing among older Zanzibari craftswomen. METHODS AND ANALYSIS: This was a cross-sectional study. Unaided and presenting distance and near vision of craftswomen 35 years and older were assessed at the women's co-operatives. We determined the number of those with distance vision poorer than 6/12 and their causes (distance-vision impairment), the number of those with near vision poorer than N8 at 40 cm (presbyopia) and the number of those whose distance and/or near-vision needs were met adequately with their habitual spectacles (effective distance and near spectacle coverages). A piloted and validated questionnaire (15 statements) was used to determine their attitude towards spectacle wearing. RESULTS: In all, 263 craftswomen participated in the survey (mean age 52.1 years±9.4 years). The prevalence of distance vision impairment among the craftswomen was 29.7% (95% CI 24.2% to 35.6%), the primary cause being uncorrected refractive error (n=51, 65.4%), and none were corrected. The prevalence of presbyopia was 86.6% (95% CI 81.5% to 90.7%, n=231) and the effective near spectacle coverage was 0.99%. The craftswomen showed a positive attitude towards spectacle wearing (strongly agree or agree) based on 12 out of 15 statements. CONCLUSION: The high burden of vision impairment, uncorrected distance refractive error and presbyopia, and a positive attitude towards spectacle wearing among older craftswomen in Zanzibar indicated the need for women-targeted eye health programmes in low-resource settings.

Caretakers' stated willingness to pay for children's spectacles in cross river state, Nigeria and its implication for a cross-subsidisation scheme: a cross-sectional study.

BACKGROUND: Understanding caretakers' willingness to pay (WTP) for their children's spectacles is essential to improving the sustainability of refractive error services and spectacle provision. Therefore, we investigated the willingness of caretakers to pay for their children's spectacles in a multi-centre study to develop a spectacle cross-subsidisation scheme in the Cross River State (CRS), Nigeria. METHODS: We administered the questionnaire to all caretakers whose children were referred from school vision screenings to four eye centres for full refraction assessment and dispensing of corrective spectacles from 9 August to 31 October 2019. We collected information on socio-demography, children's refractive error types, and spectacle prescription and then asked the caretakers about their WTP for the spectacles using a structured questionnaire and bidding format (in the local currency, Naira, ₦). RESULTS: A total of 137 respondents (response rate = 100%) from four centres were interviewed: with greater proportion of women (n = 92, 67.1%), aged between 41 and 50 years (n = 59, 43.1%), government employees (n = 64, 46.7%) and had acquired college or university education (n = 77, 56.2%). Of the 137 spectacles dispensed to their children, 74 (54.0%) had myopia or myopic astigmatism (equal to or greater than 0.50D). The mean stated WTP for the sample population was ₦3,560 (US$ 8.9) (SD ± ₦1,913.4). Men (p = 0.039), those with higher education (p < 0.001), higher monthly incomes (p = 0.042), and government employees (p = 0.001) were more willing to pay ₦3,600 (US$9.0) or more. CONCLUSION: Combining our previous findings from marketing analysis, these findings provided a basis to plan for a children's spectacles cross-subsidisation scheme in CRS. Further research will be needed to determine the acceptability of the scheme and the actual WTP.

Weight Gain and Metabolic Changes in Patients With First-Episode Psychosis or Early-Phase Schizophrenia Treated With Olanzapine: A Meta-Analysis.

BACKGROUND: Patients with first-episode psychosis or early-phase schizophrenia are susceptible to olanzapine-associated weight gain and cardiometabolic dysregulation. This meta-analysis characterized weight and metabolic effects observed during olanzapine treatment in randomized clinical trials in this vulnerable patient population. METHODS: PubMed, EMBASE, and Dialog were searched for randomized controlled trials (RCTs) reporting weight or cardiometabolic outcomes associated with olanzapine treatment in first-episode psychosis or early-phase schizophrenia. Random-effects meta-analysis and meta-regression were conducted using R v4.0.5. RESULTS: Of 1203 records identified, 26 RCTs informed the analyses. The meta-analytic mean (95% CI) weight gain was 7.53 (6.42-8.63) kg in studies (n = 19) that reported weight gain with olanzapine treatment. Stratified by duration, the mean (95% CI) weight gain was significantly higher in studies >13 weeks in duration than in those lasting ≤13 weeks: 11.35 (10.05-12.65) vs 5.51 (4.73-6.28) kg, respectively. Despite between-study variability, increases from baseline in most glycemic and lipid parameters were generally small in studies of both ≤13 and >13 weeks. There were no correlations, however, between weight gain and metabolic parameter changes when stratified by study duration. CONCLUSIONS: In RCTs enrolling patients with first-episode psychosis or early-phase schizophrenia, olanzapine was consistently associated with weight gain that was greater in studies lasting >13 weeks compared with those of ≤13 weeks. Metabolic changes observed across studies suggest that RCTs may underestimate metabolic sequelae vs real-world treatment observations. Patients with first-episode psychosis or early-phase schizophrenia are vulnerable to olanzapine-associated weight gain; strategies minimizing olanzapine-associated weight gain should be carefully considered.

How does a pair of near-vision spectacle correction empower older Zanzibari craftswomen?: A qualitative study on perception.

BACKGROUND: Studies have shown that correcting presbyopia among women could increase short-term income and quality of life. However, it is unclear whether these short-term outcomes translate to long-term empowerment. This is partly due to women's empowerment being under-studied in the eye health field. Hence, we attempted to understand Zanzibari craftswomen's perception of how near-vision spectacle correction could empower them. METHODS: Semi-structured interviews were conducted with 24 craftswomen with presbyopia (7 to 21 April 2022), identified from Zanzibari cooperatives using quota and heterogeneity sampling. We included a sample of tailors, beaders/weavers, and potters who were 40 years and older. Directed content analysis was performed on interview transcripts. RESULTS: Two themes and seven sub-themes emerged from the data. Craftswomen perceived that at the personal level, near-vision spectacle correction could improve their economic empowerment (better income and savings and buying things for themselves), psychological empowerment (more self-confidence and decision-making), political empowerment (taking up leadership roles), and educational empowerment (acquiring new skills). At a relational level, they perceived that near-vision spectacle correction could bring about economic empowerment (ability to buy things for the family), social empowerment (ability to participate in social activities), and educational empowerment (ability to educate other women). CONCLUSION: Older craftswomen perceived that correcting near vision could empower them at personal and relational levels that encompass economic, psychological, social, political and educational empowerment. The findings laid the foundation for future research into eye health and women's empowerment.

Olanzapine/Samidorphan in Young Adults With Schizophrenia, Schizophreniform Disorder, or Bipolar I Disorder Who Are Early in Their Illness: Results of the Randomized, Controlled ENLIGHTEN-Early Study.

Objective: Patients with early-phase schizophrenia or bipolar I disorder (BD-I) are at greater risk for antipsychotic-associated weight gain. This 12-week, randomized, double-blind study conducted between June 2017 and December 2021 evaluated weight effects of combination olanzapine and samidorphan (OLZ/SAM) versus olanzapine in early-phase illness.Methods: Young adults (16-39 years) with DSM-5 schizophrenia, schizophreniform disorder, or BD-I, < 4 years since symptom onset, body mass index < 30 kg/m2, and < 24 weeks' cumulative antipsychotic exposure were randomized to OLZ/SAM (5-20/10 mg/d) or olanzapine (5-20 mg/d). Primary endpoint was percent change from baseline body weight at week 12. Secondary endpoints, tested hierarchically, were proportions of patients with ≥ 10% or ≥ 7% weight gain, waist circumference change, and Clinical Global Impressions-Severity (CGI-S) change.Results: Of 428 patients (OLZ/SAM, n = 213; olanzapine, n = 215), 408 had ≥ 1 postbaseline weight assessment and were analyzed. Percent weight change was significantly lower with OLZ/SAM versus olanzapine (4.91% vs 6.77%; least-squares mean [LSM] [SE] difference, -1.87% [0.75]; P = .012). Although fewer patients treated with OLZ/SAM had ≥ 10% weight gain, the difference was not statistically significant versus olanzapine (21.9% vs 30.4%, respectively; OR = 0.64; 95% CI = 0.39 to 1.05); hierarchical testing precluded further statistical evaluation of secondary endpoints. Proportions of patients with ≥ 7% weight gain (33.1% vs 44.8%; OR = 0.61, 95% CI = 0.39 to 0.94) and waist circumference change (2.99 vs 3.90 cm; LSM [SE] difference, -0.92 cm [0.58]; 95% CI = -2.06 to 0.22) favored OLZ/SAM. LSM (SE) CGI-S change with OLZ/SAM was -0.82 (0.06). OLZ/SAM and olanzapine had similar safety profiles, including small, similar metabolic parameter changes.Conclusions: In patients with early-phase schizophrenia, schizophreniform disorder, or BD-I, OLZ/SAM treatment resulted in less weight gain versus olanzapine.Trial Registration: ClinicalTrials.gov identifier: NCT03187769.

Development of a questionnaire to assess mothers' knowledge, attitudes and practice with regard to childhood hearing loss and Universal Newborn Hearing Screening.

BACKGROUND: The assessment of the validity and reliability of measurement tools in research provides quality data. However, evidence of the validity and reliability of parental knowledge and attitude regarding childhood hearing loss and newborn hearing screening is scarce. OBJECTIVE: To design a Knowledge, Attitudes and Practice (KAP) survey tool regarding childhood hearing loss and a Universal Newborn Hearing Screening Programme of the rural Amajuba district, KwaZulu-Natal, South Africa, and then test for validity and test-retest repeatability. METHODS: Face validity was conducted with 20 mothers and a content validity index was determined by two rounds of assessments, the first by 7 experts and the second by 3 experts. The kappa statistic was used to measure the stability of the tool using data from 160 mothers where repeated measurements were applied at two-week intervals. The feasibility of developing a tool was assessed by applying the criteria of science, population and resources. RESULTS: The KAP tool was developed with twenty-nine items. For face validity, 97% of the participants reported that the items were clear, wording was appropriate and easy to read and the language was natural. Content validity produced excellent results with a scale and content validity index of 1. Test-retest repeatability for the KAP tool was good with a Cohen's kappa coefficient of 0.87 (95% CI: 0.87, 0.87). Individually, the knowledge scale had a kappa of 0.86 (95% CI: 0.77, 0.95); the attitude scale had a kappa of 0.87 (95% CI: 0.76, 0.99): the practice scale had a kappa of 0.86 (95% CI: 0.75, 0.97) and the awareness scale had a kappa of 0.92 (0.83, 1.00). The development of a KAP tool was shown to be feasible, given sufficient time, funds, motivation and a study population. CONCLUSION: The study produced a valid and reliable tool that can be useful in generating quality evidence of a community's KAP with respect to childhood hearing loss and newborn hearing screening. Evidence gathered could be used to tailor health education and health promotion material for a Universal New-born Hearing Screening (UNHS) programme in a culturally sensitive manner to promote service uptake.

Reduction in Multiple Cardiometabolic Risk Factors With Combined Olanzapine/Samidorphan Compared With Olanzapine: Post Hoc Analyses From a 24-Week Phase 3 Study.

BACKGROUND AND HYPOTHESES: Weight gain and adverse cardiometabolic effects often limit the clinical utility of olanzapine. In ENLIGHTEN-2, combining olanzapine with the opioid receptor antagonist samidorphan (OLZ/SAM) mitigated olanzapine-associated weight gain. These analyses tested the hypothesis that OLZ/SAM would be associated with reduced adverse cardiometabolic effects compared with olanzapine. STUDY DESIGN: This phase 3 double-blind study randomized adults with schizophrenia to OLZ/SAM or olanzapine for 24 weeks. Post hoc analyses assessed changes from baseline to week 24 in cardiometabolic risk parameters, including body mass index (BMI), risk of developing obesity (BMI ≥30 kg/m2) or metabolic syndrome, waist circumference, along with mean and potentially clinically significant changes in blood pressure, glucose, and lipids. RESULTS: After 24 weeks' treatment, compared with olanzapine, OLZ/SAM was associated with smaller least-squares mean (LSM) changes from baseline in systolic blood pressure (LSM difference, -2.63 mm Hg; 95% CI: -4.78, -0.47), diastolic blood pressure (LSM difference, -0.75 mm Hg; 95% CI: -2.31, 0.80), and BMI (LSM difference, -0.65 kg/m2; 95% CI: -1.01, -0.28). OLZ/SAM treatment was also associated with reduced risk of shifting from normal blood pressure to stage 1/2 hypertension (odds ratio [OR], 0.48; 95% CI: 0.24, 0.96), becoming obese (OR, 0.52; 95% CI: 0.32, 0.82), and developing metabolic syndrome (OR, 0.55; 95% CI: 0.31, 0.99) compared with olanzapine. No treatment group differences were noted for risk of hyperglycemia or hyperlipidemia. CONCLUSIONS: OLZ/SAM treatment was associated with lower risk of worsening cardiometabolic risk factors related to obesity, hypertension, and metabolic syndrome relative to olanzapine. NCT02694328, https://clinicaltrials.gov/ct2/show/NCT02694328.

Olanzapine/samidorphan combination consistently mitigates weight gain across various subgroups of patients.

OBJECTIVE: A combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) has been approved in the United States for the treatment of adults with schizophrenia or adults with bipolar I disorder. In a phase 3 study in adults with schizophrenia (ENLIGHTEN-2), OLZ/SAM treatment was associated with significantly less weight gain compared with olanzapine. Prespecified subgroup analyses explored the consistency of the weight mitigation effect of OLZ/SAM vs olanzapine across demographic subgroups in ENLIGHTEN-2. METHODS: The multicenter, randomized, double-blind ENLIGHTEN-2 study (NCT02694328) included outpatients aged 18-55 years with a diagnosis of schizophrenia based on DSM-5 criteria, a body mass index (BMI) of 18 to 30 kg/m2, and stable body weight (self-reported change ≤5% for ≥3 months before study entry). Patients were randomized 1:1 to receive OLZ/SAM or olanzapine for 24 weeks. Co-primary endpoints (previously reported) were percent change in body weight and proportion of patients with at least 10% weight gain from baseline at week 24. Prespecified exploratory subgroup analyses by sex, age, self-reported race, and baseline BMI were conducted. RESULTS: At week 24, treatment with OLZ/SAM resulted in numerically less percent weight gain than with olanzapine across all subgroups evaluated. The proportion of patients with at least 10% weight gain was smaller in each subgroup treated with OLZ/SAM vs olanzapine. CONCLUSION: In these exploratory subgroup analyses from the ENLIGHTEN-2 study, weight-mitigating effects of OLZ/SAM vs olanzapine were observed consistently across patient subgroups and were in line with results from the overall study population.

Demographic characteristics and ocular needs of children attending child eye clinics in Cross River State, Nigeria: a retrospective analysis of clinical records.

OBJECTIVES: To describe the demographic characteristics and ocular needs of children attending four child eye clinics in Cross River State, Nigeria, to inform the development of a sustainable spectacle cross-subsidisation scheme. DESIGN: Retrospective analysis of clinic records. SETTING: Four child eye clinics in Calabar, Ogoja, Ikom and Ugep, Cross River State, Nigeria, from 1 May 2017 to 30 June 2019. PARTICIPANTS: Children who failed the vision screening in schools and visited assigned child eye clinics, and self-referred children from the community. MAIN OUTCOME MEASURES: Children's age, sex, residence, diagnosis, disease management, presenting and corrected visual acuity, history of spectacle wear and magnitude of refractive errors in spherical equivalent in the worse eye. RESULTS: Of all the 3799 records reviewed, data were available for 3774 children (mean age 10.6±4.35 years; 61.6% girls; 69.1% from urban settings); 30.8% (n=1162) of them had vision impairment. Of those children, 71.2% (n=827) were diagnosed with refractive error. For management, 48.6% (n=1833) were prescribed spectacles and 40.5% (n=1527) were prescribed ocular medications. Children prescribed spectacles were significantly more likely to be girls (68.0%, p<0.001), and older than 13 years of age (53.6%, p<0.001). The most common range of spherical equivalent (in the worse eye) was <-0.50 DS to +1.75 DS (51.6%, n=945), followed by >-0.25 DS to -3.00DS (39.7%, n=727). Non-refractive eye conditions such as cataract (33.3%) and corneal disorders (14.1%) contributed to almost half of the total blindness. CONCLUSION: The findings show that spectacles provisions and ocular medications are the primary and secondary needs for children who attended child eye clinics seeking eye care services. Further research is needed to understand parents' willingness to pay for spectacles to set strategic multitier pricing for a sustainable cross-subsidisation scheme.

Fish evacuation and emergency sheltering during wildfire disasters.

Wildfires are a serious and expanding threat in western North America, and wildfire encroachment on human populations leads to widespread evacuation and emergency housing operations for residents and their companion animals and livestock. Veterinarians are frequently part of wildfire response efforts and are called upon to assist in rescue, evacuation, and emergency housing operations as well as to provide medical care for evacuated animals. Although veterinarians are likely familiar with the principles of transporting and housing terrestrial animals, emergency response for aquatic companion animals presents unique logistic challenges. Veterinarians familiar with aquatic animal evacuation, housing, and care prior to a wildfire response can extend the scope of disaster recovery. This report offers general guidance for rescuing, evacuating, housing, and caring for aquatic animals in the wake of a wildfire.

Insulin and glucose metabolism with olanzapine and a combination of olanzapine and samidorphan: exploratory phase 1 results in healthy volunteers.

A combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine's unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder.

Parents' reasons for nonadherence to referral to follow-up eye care for schoolchildren who failed school-based vision screening in Cross River State, Nigeria-A descriptive qualitative study.

BACKGROUND: Uncorrected refractive error (URE) is a major cause of vision impairment in children worldwide. Cases are often detected through a school-based vision screening program and then treated in a follow-up appointment. This requires parents or guardians ('parents') to adhere to referrals for the eye exam and care plan. We aim to understand the reasons for parents' referral non-adherence in Cross River State, Nigeria, using qualitative methods. METHODS: Ten focus groups were held with parents who had not adhered to the referral for a follow-up eye examination. Participants were recruited with help from staff in schools hosting the vision screening programme. Interviews were conducted using a semi-structured interview guide, audio taped and transcribed verbatim. After identifying relevant quotes, the researchers labelled each one with a descriptive code/subcode label. Then they clustered the data into categories and overarching themes. RESULTS: Forty-four parents participated in 10 focus group discussions with 28 women and 16 men. Three themes and participated in the focus group discussions with 28 women (63%). Twelve themes were generated. The three megathemes were Modifiable Factors (with 4 themes), Contextual Factors (with 6 themes), and Recommendations (with 2 themes). CONCLUSION: Participants identified modifiable barriers that make it difficult for parents to adhere to a referral for a follow-up eye exam. These include not believing their child has a vision problem or the screening test, and issues with the referral letter. They also described important contextual factors such as poverty, logistical problems, parental attitudes towards their children and beliefs about appropriate care. Many of these issues could be addressed by following their recommendation to educate the public on the importance of child eye care and correct parents' misconceptions. These themes will be used by the Nigerian government to enhance and scale up its child eye health programme.

Blood transcriptomics reveal the evolution and resolution of the immune response in tuberculosis.

Blood transcriptomics have revealed major characteristics of the immune response in active TB, but the signature early after infection is unknown. In a unique clinically and temporally well-defined cohort of household contacts of active TB patients that progressed to TB, we define minimal changes in gene expression in incipient TB increasing in subclinical and clinical TB. While increasing with time, changes in gene expression were highest at 30 d before diagnosis, with heterogeneity in the response in household TB contacts and in a published cohort of TB progressors as they progressed to TB, at a bulk cohort level and in individual progressors. Blood signatures from patients before and during anti-TB treatment robustly monitored the treatment response distinguishing early and late responders. Blood transcriptomics thus reveal the evolution and resolution of the immune response in TB, which may help in clinical management of the disease.

An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder.

Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is limited by the risk of significant weight gain and metabolic effects. OLZ/SAM, a combination of olanzapine and samidorphan, was recently approved in the United States for the treatment of adults with schizophrenia or BD-I. OLZ/SAM provides the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data characterizing pharmacokinetics, antipsychotic efficacy, weight mitigation efficacy, safety, and long-term treatment effects. In an acute exacerbation of schizophrenia, OLZ/SAM and olanzapine provided similar symptom improvements versus placebo at week 4. In stable outpatients with schizophrenia, OLZ/SAM treatment resulted in significantly less weight gain, reducing the risk for clinically significant weight gain and waist circumference increases of ≥5 cm by half, compared with olanzapine at week 24. Based on open-label extension studies, OLZ/SAM is safe and well tolerated for up to 3.5 years of treatment, while maintaining schizophrenia symptom control and stabilizing weight. The olanzapine component of OLZ/SAM was bioequivalent to branded olanzapine (Zyprexa); adjunctive OLZ/SAM had no clinically significant effects on lithium or valproate pharmacokinetics. Additionally, OLZ/SAM had no clinically relevant effect on electrocardiogram parameters in a dedicated thorough QT study. Overall, safety and tolerability findings from clinical studies with OLZ/SAM indicate a similar safety profile to that of olanzapine, with the exception of less weight gain. As OLZ/SAM contains the opioid antagonist samidorphan, it is contraindicated in patients using opioids and in those undergoing acute opioid withdrawal. Clinical trial results from more than 1600 subjects support the use of OLZ/SAM as a new treatment option for patients with schizophrenia or BD-I.

Factors affecting guardians' decision making on clinic-based purchase of children's spectacles in Nigeria.

BACKGROUND: This study aims to understand the key factors influencing guardians' decisions when purchasing spectacles for their children in semi-urban and urban areas of Cross River State, Nigeria, where a spectacle cross-subsidisation scheme will be implemented. METHODS: This cross-sectional study was conducted among all consecutive guardians visiting the Calabar (urban), Ugep, Ikom and Ogoja (semi-urban) public eye clinics in Cross River State, southern Nigeria, from August 1 to October 31 2019, and whose children had significant refractive errors (myopia ≤-0.50D, hyperopia ≥1.50D, astigmatism >0.75D) and received spectacles. Guardians were interviewed using a questionnaire which included i) close-ended questions on reasons guardians choose to purchase spectacles for their children in eye clinics, ii) guardians' perceptions of the quality and design of children's current spectacle, iii) factors most heavily influencing their choice of spectacles for children, and iv) open-ended questions to seek guardians' suggestions on how to improve the current spectacle range. RESULTS: All 137 eligible guardians (67.2% women [n = 92]) who visited the selected eye clinics participated in the study (response rate = 100%), with 109 (79.6%) from semi-urban and 28 (20.4%) attending urban clinics. Guardians from both urban and semi-urban clinics prioritised frame design, quality, and material as the main factors affecting their decision when purchasing spectacles for their children. Female guardians and those with higher incomes were both 1.5 times more likely to emphasise frame quality when describing selection criteria for purchasing spectacles for their children than male guardians (p = 0.01) or guardians earning less (p = 0.03). CONCLUSION: Design, material, and frame quality are key factors influencing guardians when purchasing spectacles for their children in these setting and female guardians or those with higher income prioritise frame quality. This study could guide the planning and implementation of a novel cross-subsidisation scheme in Cross River State.

Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data.

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via:  https://drinchai.shinyapps.io/BloodGen3Module/ .

Lake Michigan insights from island studies: the roles of chipmunks and coyotes in maintaining Ixodes scapularis and Borrelia burgdorferi in the absence of white-tailed deer.

Deer management (e.g., reduction) has been proposed as a tool to reduce the acarological risk of Lyme disease. There have been few opportunities to investigate Ixodes scapularis (blacklegged tick) and Borrelia burgdorferi sensu stricto dynamics in the absence of white-tailed deer (Odocoileus virginianus) in midwestern North America. A pair of islands in Lake Michigan presented a unique opportunity to study the role of alternative hosts for the adult stage of the blacklegged tick for maintaining a tick population as a deer herd exists on North Manitou Island but not on South Manitou Island, where coyotes (Canis latrans) and hares (Lepus americanus) are the dominant medium mammals. Additionally, we were able to investigate the maintenance of I. scapularis and B. burgdorferi in small mammal communities on both islands, which were dominated by eastern chipmunks (Tamias striatus). From 2011 to 2015, we surveyed both islands for blacklegged ticks by drag cloth sampling, bird mist netting, and small and medium-sized mammal trapping. We assayed questing ticks, on-host ticks, and mammal biopsies for the Lyme disease pathogen, B. burgdorferi. We detected all three life stages of the blacklegged tick on both islands. Of the medium mammals sampled, no snowshoe hares (Lepus americanus, 0/23) were parasitized by adult blacklegged ticks, but 2/2 coyotes (Canis latrans) sampled on South Manitou Island in 2014 were parasitized by adult blacklegged ticks, suggesting that coyotes played a role in maintaining the tick population in the absence of deer. We also detected I. scapularis ticks on passerine birds from both islands, providing support that birds contribute to maintaining as well as introducing blacklegged ticks and B. burgdorferi to the islands. We observed higher questing adult and nymphal tick densities, and higher B. burgdorferi infection prevalence in small mammals and in adult ticks on the island with deer as compared to the deer-free island. On the islands, we also found that 25% more chipmunks were tick-infested than mice, fed more larvae and nymphs relative to their proportional abundance compared to mice, and thus may play a larger role compared to mice in the maintenance of B. burgdorferi. Our investigation demonstrated that alternative hosts could maintain a local population of blacklegged ticks and an enzootic cycle of the Lyme disease bacterium in the absence of white-tailed deer. Thus, alternative adult blacklegged tick hosts should be considered when investigating deer-targeted management tools for reducing tick-borne disease risk, especially when the alternative host community may be abundant and diverse.

Detection of Yersinia ruckeri in Pacific Lamprey (Entosphenus tridentatus) on the Olympic Peninsula in Washington, USA.

Pacific lamprey (Entosphenus tridentatus) are important anadromous fish throughout their range in western North America. As conservation programs for lamprey expand, disease surveillance is becoming more prevalent. During routine surveillance, Yersinia ruckeri biotype II was isolated from Pacific lamprey. This is the first documented Y. ruckeri detection in Pacific lamprey.